Cephalosporin cross sensitivity with penicillin. 10%?

What we have always learnt:

  • In a patient allergic to penicillin, the cross sensitivity to any cephalosporins is 10% (it means that if you use a cephalosporin in a patient allergic to penicillin, the risk of them getting allergy is 10%)
  • Is it true?

This table answers it all.

1 2

Too complicated? let’s look at the three largest retrospective studies:


  1. Patients who reported a history of penicillin allergy may not have true penicillin allergy confirmed by skin test..
    – True penicillin allergy is IgE mediated.
    – They may have IgG or IgM reaction causing vomiting, diarrhea or non specific rash.
  2. The cross allergy between penicillin and cephalosporin is around 1%.

Let’s look at this meta-analysis by  Pichichero et al.

Cross sens of penicillin and cephalosporin in patients who reported having penicllin allergy (history alone)


Incidence rate across all generations = 96/2387 = 4%




Cross sens of penicillin and cephalosporin in a patient with penicillin allergy confirmed by skin testing:


Incidence in (+) skin test = 8/451 = 2%

  • Likely to reflect rate of cross sens closer to reality since penicillin allergy here is confirmed to be a true IgE reaction.

4s 5 6

Why is this so?

  • Cross allergy has been implicated due to similar R1 side chain (ie, cefaclor, cefadroxil, cefatrizine, cefprozil, cephalexin,and cephradine – main first and second generation cephalosporins).


  • Not all patients with history of penicillin allergy has true allergy.
  • As seen above, positive skin test to penicillin does not predict response to cephalosporins (21 cases happened in negative skin test as shown in the meta-analysis)
  • True cross allergy is only 1-4%
    – And limited to only a few first and second generation cephalosporins.
    – Basically among the lists, only Keflex (cephalexin) is commonly used now for cellulitis and osteomyelitis.
  • Avoid first and second generation cephalosporins with similar side chains. First and second generation with different side chains should be used instead.
  • Third and fourth generation cephalosporins have negligible cross sens with penicillin.



James D. Campagna, MD, Michael C. Bond, MD, Esteban Schabelman, MD, MBA, and Bryan D. Hayes, PHARMD. THE USE OF CEPHALOSPORINS IN PENICILLIN-ALLERGIC PATIENTS:A LITERATURE REVIEW. The Journal of Emergency Medicine, 2012;42(5):612-20

Michael E. Pichichero, MD, and Janet R. Casey, MD, Rochester, NY. Safe use of selected cephalosporins in
penicillin-allergic patients: A meta-analysis. Otolaryngology–Head and Neck Surgery (2007) 136, 340-347


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